Monograph on the Potential Human Reproductive and ... - OEHHA

BISPHENOL A
Table 62
Continued
Model Endpoint Value Reference
Monkeys s.c. dosed with 10 and AUC0–24 h, mg-hr/L 3247 and 39,040 a
100 mg/kg bw
Negeshi et al. (2004b).
Chimpanzees s.c. dosed with 10 mg/kg
bw
AUC0–24 h, mg-hr/L 12,492–21,141 Negeshi et al. (2004b).
Rats orally dosed with 10 mg/kg bw Apparent volume of
distribution, L/kg
4273 Yoo et al. (2001)
Immature rats orally dosed with
r10 mg/kg bw
Half-life, hr 4.3–21.8 Domoradzki et al. (2004)
Rats orally dosed with 10 mg/kg bw Terminal elimination 21.3
half-life, hr
Yoo et al. (2001)
Rats orally dosed with 10 mg/kg bw Oral clearance, mL/
min/kg
2352.1 Yoo et al. (2001)
a Results presented for low and high dose.
Table 63
Age and Route Factors Affecting Free Bisphenol A Concentrations in Blood
Model and regimen Findings for free bisphenol A in blood Reference
Age effects of rat oral dosing at 1 or 10 mg/kg: Domoradzki et al. (2004)
4 days of age 1.5–56.8 mg/L
7 days of age 1.1–12.2 mg/L
21 days of age 0.8–8 mg/L
Adulthood 0.07–0.6 mg/L
S.C. or gavage dosing of 18–21-day-old rats with [93% lower] with oral than s.c. dosing 2.9 mg/L Yamasaki et al. (2000)
160 mg/kg bw/day s.c. (plasma) 0.2 mg/L oral (plasma)
Route effects in rats administered 10 or Pottenger et al. (2000)
100 mg/kg bw:
Oral [o2–8%] BLQ (males); 0.04 mg/L (females)
(at 10 mg/kg)
s.c. [65–76%] 0.69 (males); 0.87 mg/L (females)
(at 10 mg/kg)
i.p. [27–51%] 0.39 (males); 0.34 mg/L (females)
(at 10 mg/kg)
Route effects in monkeys: Percent of dose: Kurebayashi et al. (2002)
i.v. 5–29
Oral 0–1
conjugates (Waechter et al., 2007). These considerations
taken together, suggest that it is possible that free
bisphenol A concentrations reported in biological samples
may be overestimated.
2.6.1 Toxicokinetics and metabolism. Human
toxicokinetic data for bisphenol A are summarized in
Table 60. In humans ingested bisphenol A is rapidly
glucuronidated and circulated as bisphenol A glucuronide
(Völkel et al., 2002). There is no evidence of
enterohepatic circulation (Völkel et al., 2002). Most of the
bisphenol A dose is excreted by humans through urine;
bisphenol A recoveries in urine were reported at Z84%
within 5 hr of dosing (Völkel et al., 2005) and 100% within
42 hr of dosing (Völkel et al., 2002). Human urinary
profiles were reported at B33–70% bisphenol A glucuronide,
B10–33% parent compound, and B5–34% bisphenol
A sulfate conjugate (Kim et al., 2003b; Ye et al.,
2005). The presence of bisphenol A in human fetal tissues
or fluids demonstrates that bisphenol A is distributed to
the human conceptus (Ikezuki et al., 2002; Schönfelder
et al., 2002b; Yamada et al., 2002; Kuroda et al., 2003; Tan
and Mohd, 2003; Engel et al., 2006) (Table 61). Results
from a limited number of studies indicated that fetal
bisphenol A concentrations are within the same order of
Birth Defects Research (Part B) 83:157–395, 2008
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magnitude as maternal blood concentrations (Schönfelder
et al., 2002b; Kuroda et al., 2003) and amniotic fluid
bisphenol A concentrations are B1 order of magnitude
lower than maternal blood concentrations (Yamada et al.,
2002). Significantly higher mean bisphenol A concentrations
were reported in the blood of male than female
fetuses (3.572.7 vs. 1.771.5 ng/mL, P 5 0.016). Bisphenol
A concentrations were measured in placenta samples
at 1.0–104.9, median 12.7 mg/kg (Schönfelder et al.,
2002b). There were no differences between pregnant
and non-pregnant blood levels (median in mg/L 0.44,
range 5 0.22–0.87; mean1SD 5 0.4610.20) (Kuroda et al.,
2003). Median bisphenol A concentrations in human milk
were reported to be r1.4 mg/L (Calafat et al., 2006; Ye
et al., 2006). One of the studies reported a milk/serum
ratio of 1.3 (Sun et al., 2004).
Animal toxicokinetic data for bisphenol A are summarized
in Table 62. Following oral intake of bisphenol A
by rats, most of the dose (Z77%) is glucuronidated and
circulated as bisphenol A glucuronide (Miyakoda et al.,
2000; Domoradzki et al., 2003; Kurebayashi et al., 2005).
Most bisphenol A (90–95%) circulates bound to plasma
proteins (Kurebayashi et al., 2003) [reviewed in (Teeguarden
et al., 2005)]. In a single study in mice injected